Untargeted metabolomic analysis of coronary artery disease patients with diastolic dysfunction show disturbed oxidative pathway

Abstract

Introduction: Left ventricular diastolic dysfunction (LVDD) is common in patients with coronary artery disease (CAD) with prevalence estimates of 34% and constitutes a predictor of all-cause mortality. Although diastolic dysfunction is induced by myocardial ischemia and has been shown to alter the clinical course, the role of coronary artery disease in the diastolic dysfunction and its progression into heart failure has not been completely elucidated.

Objective: The present study was conducted to identify possible metabolites in coronary artery disease patients that are differentially regulated in patients with diastolic dysfunction.

Methods: The serum of CAD (n = 75) patients and young healthy volunteers (n = 43) were analysed by using gas chromatography mass spectrometry (GC-MS) technique. Pre-processing of data results in 1547 features; among them 1064 features were annotated using NIST library.

Results and conclusion: Fifteen metabolites were found to be statistically different between cases and control. Variation in metabolites were identified and correlated with several clinically important echocardiography parameters i.e. LVDD grades, ejection fraction (EF) and E/e' values. The results suggested that metabolic products of fatty acid oxidation and glucose oxidation pathways such as oleic acid, stearic acid, palmitic acid, linoleic acid, galactose, pyruvic and lactic acids are predominantly up regulated in patients with coronary artery disease and severity of diastolic dysfunction appears to be linked to increase in fatty acid oxidation and inflammation. The metabolic fingerprints of these patients give us an insight into the pathophysiological mechanism of diastolic dysfunction in coronary artery disease patients although it did not identify validated novel markers.

Keywords: Biomarkers; Coronary heart diseases; Diastolic dysfunction; Metabolomics.